effect of intravenous ferrous sucrose on exercise capacity in chronic heart failure

Conditions: Chronic Heart Failure; Heart Diseases; Anemia, Iron-Deficiency

Summary: this is a two-center, randomised, single-blind (physician), prospective, controlled study to assess the acute (8 weeks) and chronic (16 weeks) effects of intravenous (iv) iron sucrose supplementation in anaemic and non-anaemic iron deficient patients with chronic heart failure (chf). the hypotheses are: * treatment of anaemic and non-anaemic iron-deficient chf patients with iv iron sucrose improves exercise capacity as measured by peak vo2. * iv iron sucrose is safe and well tolerated in subjects with moderate to severe chf.

study phase and design: prospective two-centre, randomized, controlled, open-label, observer-blinded, parallel-group study primary objective: to evaluate the effect of intravenous (iv) iron supplementation on exercise tolerance, as determined by peak vo2. secondary objectives: * to evaluate the effects of iv iron supplementation on exercise duration, left ventricular (lv) structure and function, symptom status (nyha class, minnesota living with heart failure questionnaire \[mlhfq\], and subjective fatigue score), and haematological and biochemical (haemoglobin \[hb\], haematocrit \[hct\], iron status, n-bnp, cytokines and oxidative stress) indices. * to evaluate the safety profile of iv iron in subjects with moderate to severe chf. sample size: 42 subjects (28 iv iron, 14 placebo); 50% anaemic and 50% non-anaemic

Eligibility criteria:
inclusion criteria: * ≥21 years of age and have signed written informed consent * stable symptomatic chf; nyha iii/iv and left ventricular ejection fraction (lvef) ≤40%, or if nyha ii then lvef must be ≤35%, as assessed within last 6 months using echocardiographic or magnetic resonance imaging techniques. * on optimal conventional therapy for at least 4 weeks prior to recruitment and without dose changes for at least 2 weeks. * peak vo2 ≤ 18 ml/kg/min on modified naughton protocol cardiopulmonary exercise testing. * mean of the 2 screening hb concentrations (week-2 and week-1) \< 12.5 g/dl (anaemic group, 50% of study population) or 12.5-14.0 g/dl (non-anaemic group, 50% of study population). * ferritin \<100 µg/l or 100-300 µg/l with tsat \<20%. * normal red cell folate and vitamin b12 status (according to local lab reference range). * resting blood pressure ≤160/100 mmhg. exclusion criteria: * history of acquired iron overload; known haemochromatosis or first relatives with haemochromatosis; and allergic disorders (asthma, eczema, and anaphylactic reactions). * known hypersensitivity to parental iron preparations. * known active infection, bleeding, malignancy and haemolytic anaemia. * history of chronic liver disease and/or alanine transaminase (alt) or aspartate transaminase (ast) \>3 times the upper limit of the normal range; chronic lung disease; myelodysplastic disorder; and known hiv/aids disease. * recipient of immunosuppressive therapy or renal dialysis. * history of erythropoietin, iv or oral iron therapy, and blood transfusion in previous 30 days. * unstable angina pectoris, as judged by the investigator; severe uncorrected valvular disease or left ventricular outflow obstruction; obstructive cardiomyopathy; uncontrolled fast atrial fibrillation or flutter (heart rate \>110 beats per minute \[bpm\]); uncontrolled symptomatic brady- or tachyarrhythmias. * musculoskeletal limitation that, in the judgement of the investigator, would impair cardiopulmonary exercise testing. * pregnant or breast-feeding * inability to comprehend study protocol * parallel participation in another clinical trial

Keywords: anaemia iron deficiency